Role of host and viral factors and genetic variation of IL28B on therapy outcome in patients with chronic hepatitis C genotype 1b from Serbia

Jovanović-Ćupić, Snežana; Petrović, Nina; Krajnović, Milena; Bundalo, Maja; Kokanov, Nikola; Božović, Ana; Stamenković, Gorana

doi:10.31383/ga.vol3iss1pp36-41

Cited by 3 publications

(2 citation statements)

References 8 publications

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“…In patients with CHC, both viral and host genetic and epigenetic factors can influence the response to therapy and progression of the liver disease [7,8]. One of the strongest host genome predictors of SVR for PEG-IFN/RBV treatment is the CC genotype of the IL28B gene, and our results are in agreement with the findings of other authors in different populations [9,10,30,31]. However, recent reports have shown that SVR does not eliminate the risk of HCC occurrence and that HCV-related epigenetic changes can persist even after treatment with antiviral therapy [6,32,33].…”

Section: Discussionsupporting

confidence: 90%

RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin

Kokanov

Krajnović

Jovanović-Ćupić

et al. 2022

ARCH BIOL SCI BELGRA

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Prevention of chronic hepatitis C (CHC) and its complications is based on antiviral therapy and early detection of reliable molecular markers in persons under risk. We investigated whether the methylation status of RASSF1A and p16 genes, alone or in combination with host and viral factors, affects the response to therapy with pegylated interferon/ribavirin (PEG-IFN/RBV). Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of the target promoter sequences of RASSF1A and p16 in circulating-free DNA from the peripheral blood of 49 patients with CHC genotype 1b. The methylation status of the examined genes did not affect the response to therapy. However, the simultaneous presence of either RASSF1A or p16 methylation and the CC genotype of IL28B was significantly related to a sustained virologic response (P=0.009 and P=0.032, respectively). After Bonferroni correction, only the result concerning the RASSF1A gene remained significant (P<0.0125). Methylation of RASSF1A was associated with the CC genotype of the IL28B gene (P=0.024) and a higher viral load (?400 000 IU/mL, P=0.009). Our results suggest that combined analysis of RASSF1A gene methylation and IL28B rs12979860 polymorphism could potentially help in the prediction of therapy response in CHC genotype 1b patients.

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Section: Discussionsupporting

confidence: 90%

RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin

Kokanov

Krajnović

Jovanović-Ćupić

et al. 2022

ARCH BIOL SCI BELGRA

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“…Genotype frequency for CC rs12979860 genotype for Serbian HCV patients was 69% (54) which was in concordance with other European populations. However, three more studies on HCV patients in Serbia reported CC rs12979860 genotype frequencies from 25-56% (55)(56)(57). Considering the fact that allele frequency of therapy non-response associated rs12979860 T allele, vary among populations (from 0% to up to 80%) and could be quite high (40% globally), distribution of rs12979860 genotypes may have an impact on outcome of ribavirin treatment.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations

Stanković¹,

Kotur²,

Gašić³

et al. 2020

J Med Biochemistry

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Background: Since there are no certified therapeutics to treat COVID-19 patients, drug repurposing became important. With lack of time to test individual pharmacogenomics markers, population pharmacogenomics could be helpful in predicting a higher risk of developing adverse reactions and treatment failure in COVID-19 patients. Aim of our study was to identify pharmacogenes and pharmacogenomics markers associated with drugs recommended for COVID-19 treatment, chloroquine/hydroxychloroquine, azithromycin, lopinavir and ritonavir, in population of Serbia and other world populations. Methods: Genotype information of 143 individuals of Serbian origin was extracted from database previously obtained using TruSight One Gene Panel (Illumina). Genotype data of individuals from different world populations were extracted from the 1000 Genome Project. Fisher’s exact test was used for comparison of allele frequencies. Results: We have identified 11 potential pharmacogenomics markers in 7 pharmacogenes relevant for COVID-19 treatment. Based on high alterative allele frequencies in population and the functional effect of the variants, ABCB1 rs1045642 and rs2032582 could be relevant for reduced clearance of azithromycin, lopinavir and ritonavir drugs and UGT1A7 rs17868323 for hyperbilirubinemia in ritonavir treated COVID-19 patients in Serbian population. SLCO1B1 rs4149056 is a potential marker of lopinavir response, especially in Italian population. Our results confirmed that pharmacogenomics profile of African population is different from the rest of the world. Conclusions: Considering population specific pharmacogenomics landscape, preemptive testing for pharmacogenes relevant for drugs used in COVID-19 treatment could contribute to better understanding of the inconsistency in therapy response and could be applied to improve the outcome of the COVID-19 patients.

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Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia

Kokanov

Jovanović-Ćupić

Šiljić

et al. 2023

ARCH BIOL SCI BELGRA

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Variations in the hepatitis C virus (HCV) core sequence have been related to disease progression and response to antiviral therapy. Previously we showed that the methylation status of RASSF1A and p16 genes, and IL28B genotypes affects the response to pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. Herein we investigated whether amino acid (aa) substitutions in the HCV core region alone or in combination with IL28B genotypes and RASSF1A/p16 methylation affect the response to PEG-IFN/RBV therapy and liver disease progression. Among 29 examined patients, we found no association between single aa substitutions and response to therapy. However, we observed that patients with the HCV core aa substitution at position 75 and CT/TT IL28B genotypes were nonresponders (NR), (P=0.023). Moreover, these patients had unmethylated RASSF1A. In contrast, most patients (75%) with aa substitutions at position 91 and CC IL28B genotype achieved sustained virologic response (SVR), (P=0.030), and 70% of them had methylated RASSF1A gene. Our results suggest that combined analysis of aa substitutions in the core protein, the IL28B rs12979860 polymorphism, and the methylation status of the RASSF1A gene may help in predicting treatment response to PEG-IFN/RBV in genotype 1b chronic hepatitis C patients.

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Role of host and viral factors and genetic variation of IL28B on therapy outcome in patients with chronic hepatitis C genotype 1b from Serbia

Cited by 3 publications

References 8 publications

RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin

RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin

Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations

Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia

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